Method of using lectins for contraception

ABSTRACT

In order to prevent conception and/or the spread of sexually transmitted diseases (STD&#39;s) one or more lectins capable of binding sperm and/or the pathogenic microorganisms responsible for STD&#39;s are administered to the vagina prior to sexual intercourse. The lectins immobilize the sperm to render them incapable of fertilization and also bind to the microorganisms to render them non-pathogenic or to the cells to prevent infection by the microorganisms. Lectins can also be administered to treat sexually transmitted vaginal infections. 
     The invention also encompasses a device for to be placed in the vault of the vagina which comprises a ring which surrounds the cervix and a membrane spanning the central aperture of the ring to prevent the direct contact of ejaculate with the cervical tissues. The device is impregnated or coated with lectins and releases them into the vaginal environment over a period of time.

This application is a continuation-in-part of application Ser. No.08/609,980 filed on Feb. 29, 1996, and now U.S. Pat. No. 5,766,632 whichis a continuation of U.S. application Ser. No. 08/462,664, filed Jun.05, 1995, abandoned, which is a divisional of U.S. application Ser. No.08/317,599, filed Oct. 03, 1994, abandoned, which is acontinuation-in-part of U.S. application Ser. No. 08/130,190, filed Oct.01, 1993, abandoned.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to methods of contraception andprophylaxis against diseases transmittable by sexual contact and therapyof such diseases, and more particularly to a method using intravaginallyadministered lectins for contraception and to protect against thetransmission of diseases that are transmissible by sexual contact and totreat such diseases. The invention also related to devices forintravaginal administration of lectins.

2. Brief Summary of the Prior Art

Sexually transmitted diseases (STD's) are epidemic in this country andworldwide. Furthermore, other diseases that have not traditionally beenconsidered to be STD's have also been found to be transmitted by sexualcontact, e.g., hepatitis B. The medical and public health problemsassociated with these epidemics have motivated a search for methods ofcontrolling these diseases by limiting their transmission from person toperson. Similarly, although many methods of contraception have beenemployed, no universally satisfactory method has been developed.

Hitherto it has been generally agreed that barrier methods which preventthe contact of body fluids between individuals are the most effectivemeans of preventing transmission of such diseases. Such barrier methodsare also effective contraceptive procedures. However, such methods aresomewhat inconvenient and require some cooperation between individuals.

An alternative method for preventing the transmission of sexuallytransmitted diseases is to kill the pathogenic microorganisms in semenand vaginal secretions so that they are incapable of invading thetissues and causing the disease. While intravaginally placedspermatocides have been used for contraception, alone or in combinationwith barrier methods, antimicrobial materials have not been so used toprevent STD's, probably because many of such materials are irritating toadjacent tissues.

Administration of biologically active materials to the vagina forwhatever purpose is usually accomplished by the use of some device thatprovides for convenient application of the medication by the userherself. A variety of devices exist for delivery of bioactive substancessuch as spermatocides and various medications. Each has its place in themedical armamentarium but each has certain deficiencies for applicationof contraceptive or anti-microbial agents in the context of sexualactivity. Conventional vaginal suppositories and ovules may not providemedication to the entire vagina because of their shape and placement bythe user in the vagina. Such suppositories are generally comprised of amaterial that melts at body temperature to allow the medication tospread and contact the tissues. However, when the dosage form melts, themedication may drain out of the vagina rather quickly, thus minimizingits potential effectiveness and significantly reducing the extendedexposure of the tissues and pathogens to the medication which is oftennecessary for effective treatment. Similarly, the effective duration ofcontraceptives applied in this way tends to be relatively brief. Inaddition, such delivery vehicles, even when freshly applied, do notprovide any physical barrier to deposition of male ejaculate on thecervix. Such ready access of sperm to the cervix may allow them toescape the action of spermatocides that are diffused throughout thevagina. Furthermore, because cells at the cervix are uniquely sensitiveto several pathogens such as Chlamydia trachomatis, the absence of abarrier deprives these cells of a significant means of protection.

In order to provide for a longer retention of medication in the vaginaand assure a more continuous delivery of active ingredients to thetissue, several types of vaginal rings have been proposed. Such devicesare disclosed, for example, in Duncan, U.S. Pat. No. 3,545,439; Roseman,U.S. Pat. No. 3,920,805; Schopflin, U.S. Pat. Nos. 4,012,496 and4,012,497; Wong et al., U.S. Pat. Nos. 4,237,885 and 4,286,587; and Nashet al., U.S. Pat. No. 4,292,965. The vaginal rings are generallyimpregnated with a spermatocide and are designed to be retained in thevaginal vault and to release the spermatocide slowly over a period oftime to maintain an effective contraceptive concentration of the activematerial in the vagina. However, such devices do not prevent the directcontact of ejaculate with the tissues of the cervix, and therefore donot protect those tissues from contact with pathogenic organisms whichmight be contained in the ejaculate. They are also of questionableefficacy in supplying the spermatocide where it is most needed.

Another approach is to use a cervical cap or a diaphragm to serve as amechanical barrier to the sperm and to dispense medication. Thesedevices are designed for a relatively tight fit either to the cervix orthe walls of the vagina to serve as a mechanical barrier to the passageof sperm. Such devices can be effective, especially as contraceptivesand when combined with spermatocides. However, because of the need toprovide a sperm-resistant seal they are frequently relatively complexdevices incorporating metallic springs within a rubber or syntheticresin structure to provide the required sealing force.

Another approach to providing an effective concentration of spermatocidein the vagina is to provide a sponge impregnated with a spermatocide.Such applicators are not intended to be precisely located and may permitthe contact of ejaculate with the tissues of the cervix, with theundesirable consequences outlined above.

Accordingly, a need has continued to exist for a method of contraceptionand prophylaxis against STD's by vaginal administration of aspermatocide and/or antimicrobial material, and for a simple andeffective device to protect the tissues at risk from contact withmicroorganisms while dispensing a spermatocidal and/or antimicrobialmaterial.

SUMMARY OF THE INVENTION

This need has now been alleviated by the method and device of thisinvention, according to which one or more lectins capable of bindingsperm and/or the pathogenic microorganisms responsible for STD's areadministered to the vagina or site of infection prior to sexualintercourse. The lectins immobilize sperm to render them incapable offertilization and also bind to the microorganisms to render themnon-pathogenic or to the cells to prevent infection by themicroorganisms.

The invention also encompasses a device for to be placed in the vault ofthe vagina which comprises a ring which surrounds the cervix and amembrane spanning the central aperture of the ring to prevent the directcontact of ejaculate with the cervical tissues. The device isimpregnated or coated with lectins and releases them into the vaginalenvironment over a period of time.

Accordingly, it is an object of the invention to provide an improvedmethod for prophylaxis against sexually transmitted diseases.

A further object is to provide a method of contraception.

A further object is to provide a method for binding and immobilizingpathogenic microorganisms in the vagina.

A further object is to provide a method for treating vaginal infections.

A further object is to provide a device for delivering lectins to thevagina over a period of time.

A further object is to provide an intravaginal device that protects thetissues of the cervix from direct contact with ejaculate.

Other objects of the invention will become apparent from the followingdetailed description when considered in conjunction with the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top plan view of a lectin-delivery device according to theinvention.

FIG. 2 is a bottom view of the lectin-delivering device of FIG. 1.

FIG. 3 is a cross section of the lectin-delivering device of FIGS. 1 and2, taken along the line 3--3.

FIG. 4 is a top plan view of another embodiment of the lectin-deliveringdevice of this invention.

FIG. 5 is a bottom view of the lectin-delivering device of FIG. 4.

FIG. 6 is a cross section of the lectin-delivering device of FIGS. 4 and5, taken along the line 6--6.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

Lectins are carbohydrate-binding proteins of nonimmune origin thatagglutinate cells or precipitate polysaccharides or glycoconjugates,i.e., proteins or lipids conjugated to oligo- or polysaccharides. Theyare widely distributed, and have been isolated from both plant andanimal sources. Their reactions with living cells are based on theirability to bind with antibody-like specificity to particulararrangements of the sugar residues that make up oligo- orpolysaccharides.

The surface of eucaryotic cells contain very numerous molecules ofglycoproteins and glycolipids. Similarly, the cell walls and outermembranes of bacteria and the envelopes of viruses contain structuralpolysaccharides and/or glycoproteins. The carbohydrate moieties of thesemolecules which are displayed on the cell surfaces exhibit great varietyin composition and structure that serves to distinguish the types ofcells and to serve as a signal to other cells or materials which comeinto contact with the cell. For, example, variation in the carbohydratemoieties of glycoproteins and glycolipids in the membrane of red bloodcells serves as the basis for the conventional blood typingclassification. When lectins recognize and bind to certain carbohydratemoieties they may serve to cross-link and agglutinate the cells bearingthe binding groups, a property that earns for them the alternate name ofagglutinins. Furthermore, because the same sort of carbohydrate moietiesoften serve as attachment points for pathogens to bind to target cellsand invade them, lectins may block infection of target cells by blockingthe sites used by pathogens as recognition markers. The same type ofspecific binding occurs between sperm and egg in conception, and can beblocked by lectins. The binding ability of lectins may be very specificfor certain mono- or oligosaccharides, allowing lectins to be used as apowerful tool for investigating the oligosaccharide epitopes on thesurface of organisms or cells. Lectins can distinguish between bloodcells of specific blood type, malignant from normal cells, and amongspecies and genus of organisms. While glycoproteins, glycolipids, andbacterial cell walls are believed to be the main lectin-bindinglocations on the surface of cells, it is not excluded that carbohydratemoieties derived from other molecules or cellular structures may bedisplayed on the cell surface or that other lectin-binding structuresmay be present on cell surfaces. All such lectin-binding structures maybe targets for the lectins used in the method of this invention.

Current medical uses of lectins include distinguishing erythrocytes ofdifferent blood types (blood typing). More recently, lectins have beenused ex-vivo in depleting T cells of patients undergoing bone marrowtransplantation.

In the context of this application the term microorganism includes anymicroscopic organism within the categories of algae, bacteria, fungi,protozoa, viruses, and subviral agents.

Among the microorganisms that are bound by certain lectins areinfectious organisms such as bacteria, protozoa, and viruses. Lectinsmay be used to identify such microorganisms in vitro and are alsocapable of binding to them in vivo, thereby preventing them frominfecting living cells. Human disease-causing organisms (and thediseases caused by them) that can be bound by lectins include Neisseriagonorrhoeae (gonorrhea); Chlamydia trachomatis (chlamydia,lymphogranuloma venereum); Treponema pallidum (syphilis); Haemophilusducreyi (chancroid); Calymmatobacterium granulomatis (donovanosis);Mycoplasma pneumoniae, M. hominis, M. genitalium, Ureaplasma urealyticum(mycoplasmas); Shigella flexneri (shigella); Salmonella typhi, S.choleraesuis, S. enteritidis (salmonella); Campylobacter fetus, C.jejuni (campylobacter); human immunodeficiency virus HIV-1 and HIV-2(HIV, AIDs); HTLV-1 (T-lymphotrophic virus type 1); herpes simplex virustype 1 and type 2 (HSV-1 and HSV-2); Epstein-Barr virus;cytomegalovirus; human herpesvirus 6; varicella-zoster virus; humanpapillomaviruses (many types) (genital warts); molluscum contagiosum(MSV); hepatitis A virus, hepatitis B virus (viral hepatitis);Trichomoniasis vaginalis (trichomoniasis); yeasts such as Candidaalbicans (vulvovaginal candidiasis). Other diseases that are transmittedby contact with bodily fluids may also be transmissible by sexualcontact and are capable of being prevented by administration of lectinsaccording to this invention. Accordingly, the term sexually transmitteddiseases (STD's) is to be interpreted in this application as includingany disease that is capable of being transmitted in the course of sexualcontact, whether or not the genital organs are the site of the resultingpathology.

Inasmuch as lectins are also capable of agglutinating human sperm andother components of the male ejaculate, and thereby rendering the spermimmobile, intravaginal administration of lectins can also serve as amethod of contraception.

According to the invention a dose of lectins adapted to bind andagglutinate pathogenic microorganisms and/or block the recognition siteson target cells is administered to the vagina prior to sexualintercourse. The active ingredients may also include lectins capable ofbinding and/or inactivating sperm or the male ejaculate to serve as acontraceptive.

Because of the specificity of lectins for certain microorganisms, it ispreferred to administer a mixture of lectins chosen for their propertiesof agglutinating specific pathogens. It is also according to theinvention to administer a mixture of sperm-agglutinating lectins andlectins capable of binding to pathogenic organisms to providesimultaneous contraception and protection against infection.

A representative listing of lectins, the abbreviations by which they arereferred to, and their sources is given in Table 1.

                  TABLE 1                                                         ______________________________________                                        Lectins and Abbreviations                                                     Lectin        Source                                                          ______________________________________                                        AAnA          Anguilla anguilla (eel serum)                                   AAurA         Aleuria aurantia (orange peel fungus)                           ABA           Agaricus bisporus (mushroom)                                    ABrA          Amphicarpanea bracteata (hog-peanut)                            AEP           Aedopodium podagraria (ground elder)                            AL            Hippaestrum hybrid (amaryllis bulbs)                            APA           Abrus precatorius (jequirity bean)                              AS            Avena sativa (oat)                                              BDA           Bryonia dioica (white bryony)                                   BPA           Bauhinia purpurea alba (camel's foot                                          tree)                                                           CA            Cymbidium species                                               CA            Colchicum autumnale (meadow saffron)                            CAA           Caragana arborescens (Siberian pea tree)                        CCA           Cancer antennarius (California crab)                            ConA          Concanavalia ensiformis (jack bean)                             CPA           Cicer arietinum (chick pea)                                     CSA           Cytisus scoparius (Scotch broom)                                DBA           Dolichos biflorus (horse gram)                                  DSA           Datura stramonium (jimson weed, thorn                                         apple)                                                          ECA           Erythrina crystagalli (coral tree)                              ECorA         Erythrina coralldendron (coral tree)                            EEA           Euonymus europaeus (spindle tree)                               EHA           Eppactus hellebrine                                             EHA           Eranthis hyamalis                                               GNA           Galanthus nivalis (snowdrop bulb)                               GSA-I/GSA-II  Griffonia simplicifolia                                         HAA           Helix aspersa (garden snail)                                    HHA           Hippeastrum hybrid                                              HPA           Helix pomatia (Roman or edible snail)                           JAC (Jacalin) Artocarpus integrifolia (jackfruit)                             LAA           Laburnum alpinum                                                LBA           Phaseolus lunatis (also limensis) (lima                                       bean)                                                           LCA (LcH)     Lens culinaris (lentil)                                         LEA           Lycopersicon esculentuin (tomato)                               LFA           Limax flavus (garden slug)                                      LOA           Lathyrus oderatus (sweet pea)                                   LDA           Listeria ovata                                                  LTA (LOTUS)   Lotus tetragonolobus (asparagus pea)                            MAA           Maackla amurensis (maackla)                                     MIH           Mangifera indica (mango)                                        MPA           Maclura pomifera (osage orange)                                 NPL (NPA)     Narcissus pseudonarcissus (daffodil)                            ORS           Oryza sativa (rice)                                             PAA           Persea americana (avocado)                                      PHA (PHA-L)   Phaseolis vulgaris (red kidney bean)                            PNA           Arachis hypogaea (peanut)                                       PSA           Pisum sativum (pea)                                             PWA           Phytolacca americana (pokeweed)                                 PTAgalactose  Psophocarpus tetagonolobus (winged bean)                        PTAgalNac     Psophocarpus tetagonolobus (winged bean)                        RCA-I/RCA-II  Ricinus communis (castor bean)                                  RPA           Robinia pseudoaccacia (black locust)                            SBA           Glycine max (soybean)                                           SJA           Sophora japonica (Japanese pagoda tree)                         SNA           Sambuccus nigra (elderberry)                                    STA           Solanium tuberosum (potato)                                     TKA           Trichosanthes kinlowii (China gourd)                            TL            Tulipa sp. (tulip)                                              TMT           Tomentine (seaweed Codium tomentosum)                           UDA           Urtica dioica                                                   UEA-I/UEA-II  Ulex europaeus (gorse or furz seeds)                            URD           Urtica dioica (stinging nettle)                                 VAA           Viscum album (European mistletoe)                               VFA           Vicia faba (fava bean)                                          VGA           Vicia graminea                                                  VRA           Vigna radiata (mung bean)                                       VSA           Vicia sativa                                                    VVA           Vicia villosa (hairy vetch)                                     WFA           Wisteria floribunda (Japanese wisteria)                         WGA           Triticum vulgaris (wheat germ)                                  suc-WGA(sWGA) Sucinyl WGA                                                     ______________________________________                                    

For example, N. gonorrheae is agglutinated by lectins that bind toN-acetyl-D-glucosamine residues on their surfaces. Such lectins includeWGA and STA, which are known to agglutinate all 193 clinical isolates ofN. gonorrhoeae. WGA is effective for such agglutination at aconcentration of 3.1 micrograms per milliliter. Other lectins showingsome agglutination activity with respect to N. gonorrhoeae includeRCA-I, RCA-II, GSA-I, and SBA.

Certain species of Chlamydia (trachomatis, psittaci, and pneumoniae) areknown to be bound by the lectins ConA, DBA, UEA-1, SBA, and PNA. WGAalso binds to the receptors on certain cells, thereby blocking infectionby C. trachomatis and C. psittaci.

PHA binds to several isolates of H. ducreyi, suggesting thatN-acetyl-D-glucosamine is present in the cell envelope polysaccharide.

WGA has been found to agglutinate a variety of bacterial cells,including Escherichia coli, Micrococcus luteus, and some types ofStaphylococcus aureus. WGA, specific for N-acetyl-D-glucosamine and SBA,specific for N-acetyl-D-galactosamine, are capable of agglutinating themany bacterial species which contain these sugar residues in their cellwall polysaccharides.

Various lectins are capable of binding to certain glycoproteins presentin the envelope of HIV virus. For example, ConA has been found to blockinfection of certain cell lines against infection by HIV in vitro, andconglutinin, a lectin derived from bovine serum, has been found to bindto the HIV envelope precursor protein gp 160, thereby preventingattachment to CD-4 receptors of target cells in vitro. GNA has beenfound to prevent infection of T-cells by HIV in vitro. Consequently,ConA, GNA and WGA have been found to be effective at preventinginfection of target cells by HIV-1 and HIV-2 in vitro. NPL andconglutinin have shown some activity as well.

HPA and ConA have demonstrated efficacy in the prevention of infectionof target cells by HSV-1 and HSV-2.

Lectins are also useful in aggregation of sperm. PHA, WGA, sWGA STA,ConA, PSA, APA, ECA, ECorA have demonstrated varying degrees of efficacyin agglutination of sperm.

While the lectins discussed above and the microorganisms and/or spermagainst which they are effective are representative of useful lectinsaccording to the invention, it is to be understood that other lectinsmay be discovered which are active in the binding and agglutination ofsperm and of the pathogens of sexually transmitted diseases, and thatthe use of such lectins is intended to be included within the scope ofthe invention.

In determining the amount of lectin to be administered for effectivebinding and/or agglutination of the pathogenic microorganisms of STD's,the amount of lectin that might be bound to vaginal tissues and therebymade unavailable for agglutination of pathogens must be considered. Instudies on murine vaginal tissue, DBA, LAA, LBA, LCA, LTA, RCA-I,RCA-II, SJA, STA, VGA, WFA have been found not to bind to the tissue atany stage of the estrus cycle. In contrast, ABA, MPA, PHA-E, PHA-L, SucConA, and WGA bound strongly to vaginal tissues at all stages of theestrus cycle. CSA, GSA-I, GSA-II, HAA, HPA, JAC, PNA, PAA, SBA, Suc WGA,UEA-I, VFA, and VVA exhibited intermediate degrees of binding to murinevaginal tissues. The amount of lectin to be administered for effectiveprophylaxis can be determined from the relative binding effect of thevarious lectins to the pathogen and to the vaginal tissues.

The selection of particular lectins to be administered will depend onthe diseases sought to be prevented. It is preferred to administer amixture of lectins, each selected for best agglutinative efficacyagainst a particular pathogen.

The lectins may be administered in any fluid or ointment vehiclesuitable for topical administration of pharmaceutical compounds. Thuscreams, ointments, foams, suppositories, liposomes, liposomes, ovulesand the like may be formulated in which the selected lectins aredispersed in a non-toxic vehicle suitable for topical and in particularfor vaginal administration. Such vehicles include oil-in-water andwater-in-oil emulsions, white petrolatum, hydrophilic petrolatum,lanolin emulsions, polyethylene glycols, cocoa butter and the like.Useful vehicles include emollient oils such as water-soluble oils, e.g.,liquid polyethylene glycols, which promote complete and uniformdistribution of the medicament within the vagina. Representativesuitable vehicles include a lubricating jelly comprised ofwater,propylene glycol, hydroxyethyl cellulose, benzoic acid and sodiumhydroxide, a water-soluble oil comprised of water, glycerin, propyleneglycol, polyquaternium #5, methyl paraben and propyl paraben; a creamcomprised of benzyl alcohol, cetearyl alcohol, cetyl esters wax,octyldodecanol, polysorbate 60, purified water, and sorbitanmonostearate; and a suppository comprised of polyethylene glycol (PEG)18, PEG-32, PEG-20 stearate, benzethonium chloride, methyl paraben andlactic acid.

Thus, the invention encompasses a composition having one or more lectinsdispersed in a pharmaceutically acceptable non-toxic vehicle. Such acomposition may be in the form of a cream, lotion, ointment, salve,foam, meltable solid, or the like.

According to the invention, the dispersion, suspension, emulsion orsolution of lectins in the vehicle may be applied to the site of alesion on the external genitalia, such as the lesions produced by herpessimplex virus type 1 or type 2, chancroid, genital warts, chancre ofsyphilis, and the like, to prevent the transfer of pathogens. Thelectins may also be introduced into the vagina in order to preventconception or infection by pathogens introduced during sexualintercourse. The amount of lectins to be applied will be an amount thatis effective to prevent conception or infection or substantially reducethe risk thereof. The amounts needed to achieve these goals will dependon the effectiveness of the individual lectins, their affinity for thetarget cell and the like. The effective amounts can be determined by theskilled practitioner by routine experimentation.

Because of their ability to bind pathogenic microorganisms, therebyinterfering with their mobility, growth and reproduction, lectins arealso useful in therapy of topical infections of the vagina. For thosediseases wherein the pathogens grow and reproduce within the lumen ofthe vagina, administration of lectins, alone or in combination withother antimicrobial materials, can assist in the treatment and cure ofthe infection.

Because some of the conventional means of administering medications tothe vagina have certain drawbacks, as discussed above, it is preferredto incorporate the lectins into a device which will remain in the vaginaand dispense the lectins over a prolonged period of time in order tomaintain an effective concentration of the lectins in the vagina. Such adevice may also be designed to provide a barrier that will prevent theaccess of pathogenic organisms into the uterus and may also function asa contraceptive device.

Thus the lectins to be introduced into the vagina can be incorporated inany conventional vaginal medication-dispensing device such assuppositories, ovules, pessaries and the like. The lectins may also beincorporated into conventional contraceptive devices such as diaphragms,cervical caps, vaginal sponges or the like. The lectins may be coated onsuch devices or linked covalently to the surface of such devices. Thecoatings or the like may be designed to release the lectins rapidly orin a controlled manner over a period of time.

The device of the invention is generally a ring of elliptical orcircular cross-section made, e.g., from a biocompatible, nontoxicthermoplastic polymer or polymeric open-cell polyurethane. Bonded to oneside of the ring or molded integral with it is a web of the samematerial.

A device according to the invention having a ring of ellipticalcross-section is illustrated in FIGS. 1-3, wherein the referencenumerals indicate the same elements in each figure. A ring 102 ofgenerally elliptical cross section constitutes the main structuralmember of the device and is sized to fit comfortably in the vaginalvault surrounding the cervix. To one side of the ring 102 is fastened arelatively thin web 104, preferably made of the same material as thering. In some embodiments the web may be molded integrally with thering.

FIGS. 4-6 illustrate another embodiment of the invention wherein a ring202, of generally circular cross section, carries a thin web 204spanning the central aperture on one side of the ring.

The device may be manufactured from any material that has been shown tobe biocompatible with the environment of the vagina and to be capable ofholding lectins within its bulk and releasing them slowly to thesurrounding environment. Several materials suitable for this functionare already known from the vaginal devices already in use or disclosedin the technical literature. Consequently, the skilled practitioner caneasily select a suitable material from which to make the device of thisinvention. The lectins may also be incorporated into a thin flexiblecoating, placed on the ring or web or both, and designed to release thelectins therefrom over a period of time, e.g., by diffusion out of thecoating or by gradual erosion and dissolution of the coating in thevaginal environment. The lectins may also be linked covalently to thesurface of the device.

The device of the invention is designed to deliver one or more lectinslocally in the vagina for:

1) contraception, by binding to the glycoproteins, glycolipids and otherglycoconjugates on the surface of sperm and by binding to theglycoproteins, glycolipids, and other glycoconjugates in the seminalfluid, thereby creating an ejaculate with significantly greaterviscosity, and thereby preventing sperm from exiting the ejaculate;

2) prophylaxis against various sexually transmitted diseases by bindingto the glycoproteins, glycolipids, and other glycoconjugates on thesurface of the bacterial agent or viral coat of the virus and theglycoproteins, glycolipids, and other glycoconjugates in the seminalfluid thereby preventing the infectious agent from reaching the targettissue;

3) prophylaxis against various sexually transmitted diseases by bindingto the glycoproteins, glycolipids and other glycoconjugate receptorsites on the vaginal stratified squamous epithelium and cervicalcolumnar epithelium, whereby the recognition sites for attack bypathogens are blocked or concealed; and

4) treatment of topical infections of the vagina by interfering with thegrowth and reproduction of the pathogenic microorganism, therebyhindering their ability to infect healthy cells.

The device of the invention also operates by providing a physicalbarrier to the direct deposition of ejaculate on the cervix. This designassures that the concentration of protective lectins in the cervicalregion will not be diluted and overwhelmed by the ejaculate. Rather, thesperm and the pathogens present in the ejaculate can only reach thecervical region gradually by diffusion and transport around the outsideof the peripheral ring of the device. This slow transport of the spermand pathogens from the ejaculate to the cervical region assures that thelectins will have an opportunity to bind to all appropriate constituentsof the ejaculate. The presence of the lectins, which will coagulate andinhibit the transport of sperm and pathogens, makes it unnecessary tohave a device that fits tightly either around the cervix or against thewall of the vagina.

Accordingly, the device of the invention has several advantages over thevaginal medication and contraceptive devices currently available:

1) It is easily inserted and comfortable to use.

2) Because of its position in the top of the vaginal canal, it ensuresthat the lectins are carried down through the vagina.

3) Since it is placed next to the cervix it can also deliver lectinstargeted to the cervix.

4) Gradual release of lectins provides a more consistent delivery overtime, thus ensuring more efficient treatment.

EXAMPLE 1

This example illustrates the utility of various lectins in binding tocertain microorganisms and to seminal plasma, sperm, human serum andcervical mucus.

The efficacy of binding of various lectins to human sperm and seminalplasma and cervical mucus, an indicator of the effectiveness of suchmaterials as vaginally-applied contraceptives, was investigated in vitroby the following procedures. Similarly the efficacy of lectin binding toNeisseria gonrrhoeae, the pathogen responsible for gonorrhoea, wasinvestigated by the following in vitro procedures. Such binding efficacyis an indication of the capability of such lectins to bind the pathogenand prevent infection when used intravaginally as a prophylacticmaterial.

Growth of Bacteria

A cervical isolate of Chlamydia trachomatis serovar G ATCC VR-878 wasgrown in McCoy cell monolayers in the presence of 1 μg of cycloheximideper ml. The culture medium was 90% Eagle's minimum essential medium-10%fetal calf serum-10 mM HEPES (pH 7.3) supplemented with 100 μg ofvancomycin per ml. Elementary bodies were purified by differentialcentrifugation followed by density gradient centrifugation In Percoll asdescribed by Newhall et al. (Newhall, W. J., Baheiger, B. and Jones, R.B. 1982, Analysis of the human serological response to the proteins ofChlamydia trachomatis, Infection Immunity 38: 1181-1189). The purifiedelementary bodies were washed twice in 10 mM HEPES-145 mM NaCl (pH 7.4)and resuspended in bicarbonate buffer (100 mM NaHCO₃ containing 0.01%NaN₃, pH 9.5). The density of elementary bodies was adjusted to aMcFarland No. 2 standard using the same buffer. Neisseria gonorrhoeaeATCC 19424 were grown on chocolate agar plates for 48-72 hrs at 37° C.in a CO₂ incubator (5% CO₂ and 80% humidity) and were harvested byscraping bacteria from the agar surface and resuspending the cells insterile phosphate buffered saline. The cells were washed three times bycentrifugation at 5000×g and resuspended in bicarbonate buffer, thedensity of which was adjusted to a McFarland No. 2 standard (opticaldensity as measured by a spectrometer--0.4 at 650 nm). The cells werestored on ice prior to immediately testing in the lectin binding assay.

Lactobacillus jensenii ATCC 25258 was grown 48-72 hrs at 37° C. in ashaking (incubator in MRS broth at pH 5.5 containing 2% glucose. Afterincubation, cells were centrifuged at 5000×g for 10 min and washed twicein phosphate buffered saline, and the density was adjusted to aMcFarland No. 2 standard with bicarbonate buffer. Haemophilus ducreyiwas grown on chocolate agar plates for 72 hrs in a CO₂ incubator (10%CO₂ and 80% humidity) t 31° C. Bacteria were harvested by scrapingbacteria from the agar surface and resuspending the cells in sterilephosphate buffered saline. The cells were washed three times bycentrifugation at 500×g, resuspended in bicarbonate buffer and the celldensity adjusted to a McFarland No.2 standard. The cells were stored onice prior to immediately testing in the lectin binding assay.

Lectin Binding Assay

Biotinylated lectins were reconstituted in phosphate buffered saline (10mM sodium phosphate-150 mM NaCl, pH 7.2) and stored in a freezer at -70°C. until used. Microtiter plates washed with 95% ethanol and dried werecoated with bacteria. (Chlamydia trachomatis or Neisseria gonorrhoeae orHaemophilus ducreyi or Lactobacillus jensenii) by adding 200 μl of abacterial suspension (in bicarbonate buffer) to each well and incubatingovernight at room temperature. Wells coated with bacteria were washedthree times In either sodium acetate buffered saline, pH 4.0, containing0.1% Tween detergent (ABST) or phosphate buffered saline containing 0.1%Tween (PBST). Lectins defrosted at room temperature were diluted in eachbuffer, and 100 μl of various lectins was added to bacteria-coated wellsat a final concentration of 50 μg/ml. After incubation in a humidchamber at room temperature for 2 hours, wells were washed three timeswith either ABST or PBST followed by the addition to each well of 100 μlof alkaline phosphatase streptavidin (10 μg/ml). After incubation for 1hour at room temperature, wells were washed three times with ABST orPBST and 100 μl of freshly prepared p-nitrophenylphosphate (1 mg/ml) in0.1 M Tris buffer-0.15 M NaCl was added and color development wasquantified with a spectrophotometer at 405 nm.

Cervical Mucus

A sample of cervical mucus was obtained from a healthy donor and the gelphase separated by centrifugation. The pellet was washed three times bycentrifugation and the mucin stabilized and alkylated before dialysisagainst a low ionic strength, pH 8.0 buffer. The cervical mucus wasbound to flat-bottomed plates by incubating in bicarbonate coatingbuffer at 4° C. overnight. The plates were washed to remove unboundligand. Biotinylated lectins were serially diluted across the plates inthe wash buffer and the plates incubated at room temperature for 2 hrs.Unbound lectin was removed by washing, and the bound lectins were taggedby incubating with streptavidin-alkaline phosphatase at room temperaturefor 1 hr. Unbound streptavidin-alkaline phosphatase was removed bywashing and the assay completed by adding freshly preparedp-nitrophenylphosphate (1 mg/ml) in 0.1 M Tris buffer-0.15 M NaCl) andmonitoring the rate of color production.

Seminal Plasma and Sperm

A sample of ejaculate was donated by a healthy donor and the seminalplasma (supernatant) removed by centrifugation and frozen at -20° C. Thebinding assay was performed in the same way as for cervical mucus.

The sperm pellet resulting from centrifugation of the ejaculate waswashed twice and total sperm count determined using a hemocytometer.Sperm were added to plates, left to settle at room temperature for 2 hrsand fixed using glutaraldehyde. The plates were then washed and unboundsites blocked with protein solution and stored at +4° C. until use. Theremainder of the binding assay was performed in the same way as forcervical mucus and seminal plasma.

Serum

A sample of blood was collected from a healthy donor, the serumseparated by centrifugation and stored at -20° C. The binding assay wasperformed in the same way as for cervical mucus an d seminal fluid.

Analysis of Data

Sigma Plot was used for graphing and curve fitting of binding plots.Velocity of the color-forming reaction versus concentration of lectinadded was plotted. Binding curves were fitted to the hyperbolic equationf(x)=ax/(b+x) where "x" is the concentration of lectin, "f(x)" is therate of reaction measured by change in optical density (OD) of thereaction solution per unit time, "a" is the asymptotic value of maximumreaction velocity measured as change in optical m_(OD) /min) and "b" isthe concentration of lectin where half of maximum binding occurs(represented in the following tables as [Lectin]_(1/2max)). The binding"quotient" is defined as a/b.

The data for lectin binding to sperm, seminal plasma, cervical mucus,human serum, Neisseria gonrrhoeae, and Lactobacillus jensenii aresummarized in the following tables.

                  TABLE 2                                                         ______________________________________                                        SUMMARY OF BINDING DATA                                                                                     QUOTIENT                                                             Seminal  Cervical Human                                  Lectin      Sperm    Plasma   Mucus    Serum                                  ______________________________________                                        ABA         WB       0.44     WB       WB                                     AL          NB       NB       NB       NB                                     BPA         0.60     0.86     20.76    WB                                     CAA         0.46     1.04     7.82     WB                                     ConA        2.59     2.68     1.11     3.29                                   CPA         WB       WB       WB       WB                                     CSA         WB       0.30     7.30     WB                                     DBA         WB       WB       WB       WB                                     DSA         1.09     WB       WB       WB                                     ECA         WB       WB       WB       WB                                     EEA         NB       NB       0.39     NB                                     GNA         0.36     0.58     0.24     WB                                     GSA-I/GSA-II                                                                              WB       WB       WB       WB                                     HAA         NB       WB       WB       WB                                     Jacalin     3.43     11.63    21.55    8.93                                   LAA         NB       0.57     WB       WB                                     LBA         WB       WB       WB       WB                                     LcH         7.26     2.58     8.64     1.60                                   LES         WB       WB       WB       WB                                     LOTUS       NB       0.94     4.13                                            MAA         NB       WB       WB       NB                                     MPA         2.29     3.17     13.8     1.18                                   NPA         NB       NB       NB       NB                                     PWA         WB       NB       NB       NB                                     PHA-L       WB       WB       WB       NB                                     PNA         WB       WB       7.25     NB                                     PSA         3.44     2.70     14.5     1.12                                   PTAgalactose                                                                              NB       WB       1.31     WB                                     PTAgalNacnb NB       NB       1.39     WB                                     RPA         1.28     0.84     0.45     WB                                     SBA         NB       WB       WB       NB                                     SJA         NB       WB       WB       NB                                     STA         NB       WB       WB       NB                                     sWGA        1.32     7.50     WB       WB                                     TKA         WB       0.87     WB       WB                                     UEA-1       WB       WB       14.72    WB                                     VPA         WB       2.78     5.21     2.02                                   VRA         WB       3.35     WB       WB                                     VVA         N/A      0.81     WB       WB                                     WFA         2.48     1.96     26.24    WB                                     WGA         19.38    4.87     12.77    1.13                                   ______________________________________                                         Notes                                                                         1. N/A  not available                                                         2. NB  no binding                                                             3. WB  weak binding                                                      

                  TABLE 3                                                         ______________________________________                                        LECTIN BINDING TO SPERM                                                               Max          [Lectin].sub.1/2 Max                                     Lectin  (m.sub.OD /min)                                                                            (μg/ml) Quotient                                      ______________________________________                                        WGA     155          8          19.38                                         LcH     196          27         7.26                                          PSA     141          41         3.44                                          Jacalin 103          30         3.43                                          ConA    57           22         2.59                                          WFA     67           27         2.48                                          MPA     48           21         2.29                                          sWGA    41           31         1.32                                          RPA     120          94         1.28                                          DSA     63           58         1.09                                          BPA     67           112        0.60                                          CAA     33           71         0.46                                          GNA     27           74         0.36                                          ______________________________________                                    

                  TABLE 4                                                         ______________________________________                                        LECTIN BINDING TO SEMINAL PLASMA                                                      Max          [Lectin].sub.1/2 Max                                     Lectin  (m.sub.OD /min)                                                                            (μg/ml) Quotient                                      ______________________________________                                        Jacalin 93           8          11.63                                         sWGA    45           6          7.50                                          WGA     112          23         4.87                                          VRA     208          62         3.35                                          MPA     57           18         3.17                                          VFA     125          45         2.7                                           PSA     100          37         2.70                                          ConA    51           19         2.68                                          LcH     147          57         2.58                                          WFA     49           25         1.96                                          CAA     51           49         1.04                                          LOTUS   32           34         0.94                                          BPA     64           74         0.86                                          RPA     56           64         0.88                                          VVA     25           31         0.81                                          GNA     38           65         0.58                                          TKA     39           45         0.87                                          LAA     37           65         0.57                                          ADA                             0.44                                          CSA     25           82         0.30                                          ______________________________________                                    

                  TABLE 5                                                         ______________________________________                                        LECTIN BINDING TO CERVICAL MUCUS                                                         Max        [Lectin].sub.1/2 Max                                    Lectin     (m.sub.OD /min)                                                                          (μg/ml) Quotient                                     ______________________________________                                        WFA        656        25         26.24                                        Jacalin    237        11         21.55                                        BPA        353        17         20.76                                        UEA-1      265        18         14.72                                        PSA        58         4          14.50                                        MPA        138        10         13.80                                        WGA        562        44         12.77                                        LcH        121        14         8.64                                         CAA        352        45         7.82                                         CSA        445        61         7.30                                         PNA        174        24         7.25                                         VFA        203        39         5.21                                         LOTUS      194        47         4.13                                         PTAgalNac  110        79         1.39                                         PTAgalactose                                                                             113        86         1.31                                         ConA       41         37         1.11                                         RPA        25         56         0.45                                         EEA        27         70         0.39                                         GNA        13         55         0.24                                         ______________________________________                                    

                  TABLE 6                                                         ______________________________________                                        LECTIN BINDING TO HUMAN SERUM                                                         Max          [Lectin].sub.1/2 Max                                     Lectin  (m.sub.OD /min)                                                                            (μg/ml) Quotient                                      ______________________________________                                        Jacalin 134          15         8.93                                          ConA    79           24         3.29                                          VFA     107          53         2.02                                          LcH     123          77         1.60                                          MPA     40           34         1.18                                          WGA     160          142        1.13                                          PSA     84           75         1.12                                          ______________________________________                                    

                  TABLE 7                                                         ______________________________________                                        LECTIN BINDING TO NEISSERIA GONORRHOEAE                                       pH 4                                                                                  Max          [Lectin].sub.1/2 Max                                     Lectin  (m.sub.OD /min)                                                                            (μg/ml) Quotient                                      ______________________________________                                        BPA     1190         82         14.51                                         CPA     80           33         2.42                                          CSA     560          7          80.00                                         GNA     294          18         16.33                                         LAA     176          42         4.19                                          LBA     275          14         19.64                                         LCH     213          176        1.21                                          LEA     106          7          14.29                                         MAA     235          56         4.20                                          MPA     159          5          31.80                                         NPA     299          38         7.87                                          PSA     55           13         4.23                                          RPA     233          10         23.30                                         SBA     414          8          51.75                                         STA     194          24         7.57                                          sWGA    49           0.50       90.00                                         TKA     178          55         3.24                                          VVA     411          3          137.00                                        WEA     331          3          110.33                                        WGA     125          0.78       160.26                                        ______________________________________                                    

                  TABLE 8                                                         ______________________________________                                        LECTIN BINDING TO LACTOBACILLUS JENSENII                                              Max          [Lectin].sub.1/2 Max                                     Lectin  (m.sub.OD /min)                                                                            (μg/ml) Quotient                                      ______________________________________                                        ABA     216          2          108.00                                        BPA     557          57         9.77                                          GNA     405          12         33.75                                         Jacalin 148          7          21.14                                         LBA     334          15         22.27                                         RPA     177          55         3.22                                          SBA     523          63         8.30                                          WFA     464          23         20.17                                         STA     140          19         7.37                                          LEA     45           82         0.55                                          DSA     26           80         0.33                                          MPA     2047         328        6.24                                          ConA    301          7          43.00                                         sWGA    96           64         1.50                                          LAA     136          17         8.00                                          CSA     624          387        1.61                                          NPA     425          36         11.81                                         VVA     260          33         7.88                                          ______________________________________                                    

In the above tables the affinity of the lectin for a particularsubstrate is inversely proportional to the maximum velocity of thecolor-forming reaction. Consequently, those lectins having a smaller bvalue ([lectin]_(1/2max)) bind more firmly to the substrate. A highbinding efficacy (low m_(OD) /min) is preferable for binding to sperm orseminal plasma for contraceptive purposes or to a pathogen, such asNeisseria gonorrhoeae, whose infections activity is to be inhibited.However, it must be recognized that some microorganisms of the vaginalflora, e.g., Lactobacillus jensenii, are desirable and may even providesome protection against pathogenic organisms. Accordingly, if possible,it is desirable to select a lectin for contraception and/or prophylaxisagainst sexually transmitted diseases that combines great bindingaffinity for the constituents of the male ejaculate or for a pathogenicmicroorganism, but has a lesser, preferably minimal, binding affinityfor beneficial vaginal flora. A skilled practitioner may select the mostefficacious lectins by consulting the data provided in the tables ofthis example.

EXAMPLE 2

This example illustrates the effectiveness of lectins in inhibiting theinfective activity of Chlamydia trachomatis.

Chlamydia trachomatis serovar G was cultured as described in Example 1.Lyophilized lectins were reconstituted in phosphate buffered saline(PBS) to a concentration of 1 mg/ml and frozen at -20° C. The lectinswere prepared for testing in the Chlamydia trachomatis inactivationassay by diluting them in McCoy growth medium (MEM) to appropriateconcentrations. Chlamydia trachomatis serovar G was added to the dilutedlectins and the mixture was incubated for 1 hour at 37° C. Afterincubation, the Chlamydia-lectin mixture was added to McCoy cells in15×45 mm shell vials and centrifuged at 3500×g for 60 minutes at 37° C.Following centrifugation, the medium in the vials was removed and 1 mlof Chlamydia overlay medium (with cycloheximide) was added to each vial.The vials were incubated for 42-43 hours and the cells were then fixedand stained for Chlamydia trachomatis using Syva Microtrak™ Chlamydiatrachomatis culture confirmation reagent.

Samples of the infected cell culture were then examined under themicroscope and evaluated for the effect of the lectin on the infectivityof the microorganism. Table 9 shows the number of Chlamydia trachomatisinclusions per 160× microscopic field on a 12 mm circular glasscoverslip as a percentage of a positive control sample which was notexposed to any lectins. WGA (118%) and ConA (121%) show enhancedinfectivity of Chlamydia trachomatis serovar G in having more inclusionsper 160× field than the positive control which had not been exposed toany lectins. In contrast, exposure to Jacalin shows significantlyreduced infectivity of Chlamydia trachomatis serovar G as evidenced bythe 65% reduction in the number of inclusions per 160× field (35% of thepositive control value).

                  TABLE 9                                                         ______________________________________                                        Lectin       Concentration                                                                            Infectivity                                           ______________________________________                                        ABA          150        59                                                    TKA          150        80                                                    WGA          50         118                                                   DSA          50         75                                                    WFA          150        48                                                    VFA          150        61                                                    ConA         150        121                                                   Jacalin      150        35                                                    MPA          150        55                                                    ______________________________________                                    

EXAMPLE 3

This example illustrates the effectiveness of lectins in blocking theinfectivity of human immunodeficiency viruses Type 1 and 2(HIV-1/HIV-2).

The effect of lectins on the infectivity of HIV-1 and HIV-2 toward humanlymphocytes was investigated in vitro by a standard technique (Balzariniet al. 1991, Antimicrobial Agents and Chemotherapy, March 1991, pages410-416) wherein the toxicity of the lectins toward the infected cellswas determined (human T-lymphocytes CEM/0) and also the ability of thelectins to block the fusion of infected cells (HUT-78/HIV-1(III_(B)))with other cells (MOLT/4 clone 8). The results of these tests are setforth in Tables 10 and 11 below. The results are expressed in terms ofthe concentration of lectins required to reduce by 50% the number ofviable cells in the virus-infected cell cultures (EC₅₀) and in thecontrol cell cultures (mock-infected) (CC₅₀), respectively.

                                      TABLE 10                                    __________________________________________________________________________    Anti-HIV-1 and -HIV-2 Activity and cytotoxicity of                            Lectins in Human T-Lymphocyte (CEM/0) Cells                                          EC.sub.50.sup.a (μg/ml)                                             Compound                                                                             HIV-1      HIV-2      CC.sub.50.sup.b (μg/ml)                       __________________________________________________________________________    ABA    >100 - >100                                                                              >100 - >100                                                                              83 - 62                                                 >100       >100       73 ± 15                                       CAA    >100 - >100                                                                              >100 - >100                                                                              140 - >200                                              >100       >100       ≧140                                      ConA   2.4 - 0.8 - 1.4                                                                          1.8 - 0.8 - 2.4                                                                          20 - 19                                                 1.5 ± 0.79                                                                            1.4 ± 0.77                                                                            20 ± 0.71                                     CPA    >100 - >100 - >100                                                                       >100 - >100 - >100                                                                       >200 - >200 - >200                                      >100       >100       >200                                             CsA    >100 - >100 - >100                                                                       >100 - >100 - >100                                                                       >200 - >200 - >200                                      >100       >100       >200                                             DSA    >20        >20        >10.5                                            ECA    >100 - >100                                                                              >100 - >100                                                                              12-15                                                   ≧100                                                                              ≧100                                                                              14 ± 2.5                                      EEA    >0.16 - >0.16                                                                            >0.16 - >0.16                                                                            0.47 - 0.53                                             >0.16      >0.16      0.50 ± 0.04                                   GSA-I  >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             GSA-II >100 - >100 - >100                                                                       >100 - >100 - >100                                                                       90 - >200 - >200                                        >100       >100       ≧90                                       HAA    20 - 9     11.5 - 11.5                                                                              9.7 - 18                                                15 ± 7.8                                                                              11.5       14 ± 5.9                                      JAC    >20 - >20  >20 - >20  16 - 27                                                 >20        >20        22 ± 7.4                                      LAA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             LBA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             LCH    9 - 4 - 20 >100 - >100 - >100                                                                       17 - 17 - 12                                            11 ± 8.2                                                                              >100       15 ± 2.9                                      LEA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             Lotus  >100 - >100                                                                              >100 - >100                                                                              90 - >200 - >200                                        >100       >100       ≧90                                       MPA    >0.8 - >4  >0.8 - >4  6.8 - 11                                                >0.8       >0.8       8.9 ± 3.0                                     PAA    >100 - >100                                                                              >100 - 58  >200 - >200                                             >100       ≧58 ±140                                          PHA-L  11.5 - 11.5 - 45                                                                         >100 - >100 >100                                                                         11 - 23                                                 23 ± 19 >100       17 ± 8.5                                      PNA    >100 - >20 - >20                                                                         >100 - >20 - >20                                                                         95 - 80                                                 >20        >20        88 ± 11                                       PSA    20 - 9 - 20 - 45                                                                         45 - 100 - 100                                                                           25 - 17                                                 16 ± 6.4                                                                              82 ± 32 21 ± 5.7                                      PTAgal >100 - >100 - >100                                                                       >100 - >100 - >100                                                                       >200 - >200                                             >100       >100       >200                                             PTAgalNac                                                                            >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             SJA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             sWGA   >100 - >100                                                                              >100 - >100                                                                              -200 - >200                                             >100       >100       >200                                             TKA    >100 - >100                                                                              >100 - >100                                                                              100 - 95                                                >100       >100       98 ± 3.5                                      UEA-1  >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             VFA    9 - 34 - 38                                                                              >100 - >100 - 100                                                                        120 - 77 - 95                                           34 ± 25 ≧100                                                                              97 ± 22                                       VVA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             WFA    >100 - >100                                                                              >100 - >100                                                                              >200 - >200                                             >100       >100       >200                                             WGA    11.5 - 20 - >20                                                                          9 - >20 - 20                                                                             11.5 - 15                                               ≧16 ± 6.0                                                                      ≧15 ± 7.8                                                                      13 ± 2.5                                      __________________________________________________________________________     .sup.a Effective concentration or concentration required to protect CEM       cells against the cytopathogenicity of HIV by 50%.                            .sup.b Cytotoxic concentration or concentration required to reduce CEM        cell viability by 50%.                                                        *Cluster formation of the cells after 4 days incubation with the compound

                  TABLE 11                                                        ______________________________________                                        Inhibitory Effect of Lectins on Giant Cell Formation Between                  HUT-78/HIV-1(III.sub.a) and MOLT/4 clone 8 cells                                            EC.sub.50 (μg/ml)                                            Compound      Individual Values                                                                            Average                                          ______________________________________                                        ABA           >100 - >100    >100                                             CAA           >100 - >100    >100                                             ConA          1.7 - 9        5.4 ≧ 5.2                                 CPA           >100 - >100    >100                                             CSA           >100 - >100    >100                                             ECA           >100 - >100    >100                                             EEA           >4 - >4        >4                                               GSA-I         >100 - >100    >100                                             GSA-II        >100 - >100    >100                                             HAA           >100 - >100    >100                                             JAC           >100 - >100    >100                                             LAA           >100 - >100    >100                                             LBA           >100 - >100    >100                                             LCH           45 - 45        45                                               LEA           >100 - >100    >100                                             Lotus         >100 - >100    >100                                             MPA           >100 - >100    >100                                             PAA           >100 - >100    >100                                             PHA-L         44 - 12 - 44   33 ± 18                                       PNA           >100 - >100    >100                                             PSA           45 - 58 - 58   54 ± 7.5                                      PTAgal        >100 - >100    >100                                             PTAgalNac     >100 - >100    >100                                             SJA           >100 - >100    >100                                             sWGA          >100 - >100    >100                                             TKA           >100 - >100    >100                                             UEA-I         >100 - >100    >100                                             UFA           >100 - >100    >100                                             VVA           >100 - >100    >100                                             WFA           >100 - >100    >100                                             WGA           20 - >4        ≧20                                       ______________________________________                                         *Cluster formation of the cells after 1 day incubation with the compound 

The invention having now been fully described, it should be understoodthat it may be embodied in other specific forms or variations withoutdeparting from its spirit or essential characteristics. Accordingly, theembodiments described above are to be considered in all respects asillustrative and not restrictive, the scope of the invention beingindicated by the appended claims rather than by the foregoingdescription, and all changes which come within the meaning and range ofequivalency of the claims are intended to be embraced therein.

We claim:
 1. A method of contraception comprising administering to thevagina an amount of a composition containing at least one lectin capableof agglutinating sperm or other components of male ejaculate sufficientto render said sperm incapable of fertilization, said lectin beingdispersed in a biocompatible non-toxic vehicle, and said lectin beingselected from the group consisting of AS, NPA, ORS, STA, PAA, LOA, andLEA.
 2. The method of claim 1 wherein a plurality of lectins isadministered.
 3. A composition for administering lectins to the vaginacomprising at least one lectin dispersed in a pharmacologicallyacceptable non-toxic vehicle.
 4. The composition of claim 3 containing aplurality of lectins.
 5. The composition of claim 3 wherein said lectinis selected from the group consisting of WGA, LcH, PSA, Jacalin, ConA,AS, WFA, MPA, sWGA, RPA, DSA, BPA, CAA, GNA, VRA, VFA, LOTUS, NPA, VVA,TKA, LAA, ABA, CSA, UEA-1, PNA, PTAgalNac, PTAgalactose, EEA, ORS, STA,PAA, LOA, and LEA.
 6. The composition of claim 5 containing a pluralityof lectins.
 7. A device for administering lectins to the vaginacomprising a solid support adapted to be inserted into the vagina, saidsupport being impregnated with or coated with at least one lectin. 8.The device of claim 7 wherein a plurality of lectins are impregnatedtherein or coated thereon.
 9. The device of claim 7 wherein said lectinis selected from the group consisting of WGA, LcH, PSA, Jacalin, ConA,AS, WFA, MPA, sWGA, RPA, DSA, BPA, CAA, GNA, VRA, VFA, LOTUS, NPA, VVA,TKA, LAA, ABA, CSA, UEA-1, PNA, PTAgalNac, PTAgalactose, EEA, ORS, STA,PAA, LOA, and LEA.
 10. The device of claim 9 wherein a plurality oflectins are impregnated therein or coated thereon.